Introduction

Major depressive disorder (MDD) is a prevalent mental health disorder affecting approximately 280 million people worldwide, making it the third leading cause of disease burden globally. The World Health Organization (WHO) predicts that it will become the leading cause of disease burden by 2030(G.D.a.I. Collaborators, 2020). The global pandemic of COVID-19 has worsened many factors that contribute to mental health deterioration. This has led to a sustained increase in the prevalence of MDD, reaching 5% globally. The prevalence of MDD is high, affecting nearly one in 10 adults and up to 17% of adolescents in North America (Goodwin et al., 2022), about 7% in Europe (Arias-de la Torre et al., 2021), and as high as 34% in Asia-Pacific (Balakrishnan et al., 2022). The main symptoms of depression include a depressed mood, loss of energy, irritability, decreased appetite, and sleep disorders. In severe cases, MDD can damage both the central and peripheral nervous systems, affecting normal cognitive function and potentially leading to self-harm and suicidal ideation (Malhi and Mann, 2018). Approximately 71% of patients experience treatment-resistant depression (TRD), which can lead to irreversible psychological trauma if left untreated. This can cause significant burdens for individuals, families, and society. Timely intervention is crucial to prevent symptom exacerbation (Kulkarni et al., 2020).

Currently, drug therapy is the primary intervention for MDD. However, it is affected by side effects, addiction, and drug resistance, resulting in unsatisfactory overall efficacy. Additionally, it can cause a substantial increase in sedentary behavior, which can seriously affect the mental health and quality of life of patients (Almohammed et al., 2022). Cure rates for MDD remain low, with approximately 60% of patients worldwide not receiving adequate treatment (Mekonen et al., 2021). Therefore, some researchers have investigated alternative treatments for MDD. One such treatment is physical activity (PA), which has been shown to be an effective non-pharmacological intervention. PA not only reduces negative emotions and related symptoms, but also improves cognitive functioning and sleep quality. Its efficacy is comparable to that of drugs (Netz, 2017). However, research suggests that there may be variations in the physiological and psychological responses triggered by different types, durations, and intensities of PA (van Baak et al., 2021). For example, the American College of Sports Medicine (ACSM) categorizes PA into continuous endurance training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind–body training (MBT) in the ACSM Guidelines for Exercise Testing and Prescription. training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind–body training (MBT) (Thompson et al., 2022). Research suggests that EIT and RST have the most significant moderating effects on acute mood and sleep quality in patients with MDD (Singh et al., 2023). In contrast, ECT and MBT were more beneficial for maintaining exercise adherence and cognitive function (Schuch et al., 2016). To date, the number of studies investigating the dosage profile of different PAs in MDD interventions is still limited, and the associated neural and physiological underpinnings have not been elucidated.

This paper explores the quantitative and temporal effects of different PA on the antidepressant process. It compares the effects of various forms, durations, and intensities of PA in improving the related symptoms, cognitive functions, and sleep status of patients with MDD. Additionally, it analyzes the possible mechanisms and physiological bases of these effects. The aim of this paper is to provide effective recommendations and theoretical references for exercise prescription in future MDD treatment and intervention.

Clinical symptoms and pathology of MDD

The primary symptoms of MDD are one of the leading causes of disease burden and disability worldwide and top the list of mental disorders (Dubovsky et al., 2021). The primary symptoms of MDD include persistent depressed mood, cognitive decline, autonomic dysfunction, and reduced quality of life. MDD includes bipolar II depression, mixed depression, agitated depression, atypical depression, melancholic depression, recurrent brief depression, minor depressive disorder, seasonal affective disorder, and other disorders (Benazzi, 2006). Research has shown that MDD is detrimental to both mental health and physical functioning. In terms of brain health, long-term MDD can lead to cognitive decline in executive function, memory, and inhibition, as well as a variety of neurodegenerative diseases, including Alzheimer’s disease, dementia with Lewy bodies, frontotemporal lobe dementia, and Parkinson’s disease (PE, 2015). Physically, MDD can lead to abnormalities in BMI, sinus rhythm, and immune function, as well as an increased risk of metabolic syndrome and cardiovascular disease (Vancampfort et al., 2015). In terms of mental health, MDD can be characterized by chronic depression, anxiety, or stress, as well as decreased self-esteem, self-efficacy, and self-control (LeMoult and Gotlib, 2019).

Regarding brain structure, MDD episodes are closely associated with a reduction in brain volume and changes in brain structure. Patients with MDD have been found to have abnormalities in the volume of frontal, temporal, thalamus, hippocampus, striatum, and amygdala structures (Koolschijn et al., 2009; Yaghmaei et al., 2009). Additionally, increased thickness of the temporal pole, right/left frontal gyrus, and paracentral region have been observed (Peng et al., 2015). There was a significant decrease in gray matter density in the hippocampus, amygdala (Espinoza Oyarce et al., 2020; Binnewies et al., 2021), and prefrontal cortex (PFC), as well as damage to white matter fiber tracts in frontal, parietal, and temporal regions. These changes were specifically reflected in the decline of cognitive function, memory, and executive function (Bora et al., 2012). For instance, a study discovered that while the whole brain volume of patients with MDD was not significantly different from that of healthy individuals, the hippocampal volume was significantly lower and the caudate nucleus was larger (Schmaal et al., 2016). This was particularly prominent in cases of chronic or recurrent depression and showed abnormalities in emotion regulation (Schmaal et al., 2016). One of the important hallmarks of MDD is a decrease in the volume of the striatum and paleostriatum (Wade et al., 2016). The patient’s deficits in interest were also contributed to by abnormalities in connectivity between the ventral striatum and several brain regions involved in reward processing (Pan et al., 2022). And this phenomenon is more severe in later life (Bora et al., 2012). Furthermore, research has shown that the severity of MDD is linked to decreased activity in the amygdala (Ferri et al., 2017). A study found that training to improve the amygdala’s response to positive memories significantly reduced depressive symptoms (Young et al., 2017).

Regarding the intracranial environment and plasticity, changes in the brain environment, certain nerve cells, neurotransmitters, and small molecules are closely linked to MDD. Studies have shown that patients with MDD have reduced neuron volume and glial cell density in PFC (Rajkowska et al., 1999). This is mainly due to the fact that MDD induces higher cortisol levels in the hippocampus, which in turn impedes neuronal growth in the brain (Lebedeva et al., 2018). Multiple studies have found that MDD is associated with imbalanced and reduced levels of neurotransmitters such as 5-hydroxy tryptamine (5-HT), norepinephrine (NE), brain-derived neurotrophic factor (BDNF), and dopamine (DA) in the brain. These imbalances lead to reduced nerve fiber conductivity and negatively impact an individual’s cognitive abilities and thought processes (Lima Giacobbo et al., 2019). Furthermore, there is evidence suggesting that the pathophysiology of MDD may be related to decreased levels of glutamate (Glu) metabolites in the medial frontal cortex and increased levels of acetylcholine (Moriguchi et al., 2019). Also based on the gamma-aminobutyric acid (GABA) hypothesis of MDD (Möhler, 2012), there are studies that have found lower levels of GABA within the cerebrospinal fluid and plasma of human and animal models of MDD (Streeter et al., 2020). On the other hand, increased peripheral and central inflammatory cytokines, acute phase protein (APP), and oxidative stress (OS) are also major markers of an abnormal intracranial environment in individuals with MDD (Troubat et al., 2021). Research has demonstrated that MDD is linked to elevated levels of inflammatory cytokines, including Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-alpha), in the brain. These cytokines are known to regulate mood, appetite, and sleep (Goshen et al., 2008; Haapakoski et al., 2015). In addition, the involvement of OS in the pathogenesis of MDD is well established. The brain is particularly susceptible to OS due to its high oxygen and lipid content, but weak antioxidant capacity (Bhatt et al., 2020). OS also plays an important role in the pathophysiology of MDD through free radicals/nonradical molecules and reactive oxygen/nitrogen species (Vaváková et al., 2015).

Dose characterization of PA in MDD interventions Differences in exercise patterns in relieving depression levels Endurance continuous training

ECT is also known as aerobics exercise (AE) or moderate-intensity continuous training (MICT) that utilizes oxygen as a metabolic pathway to meet the body’s energy needs through oxidative phosphorylation. This type of exercise also leads to lower blood lactate levels (Hargreaves and Spriet, 2020). ECT is typically characterized by repeated moderate-intensity physical activity over a prolonged period, usually greater than 30 min. The intensity of ECT is typically in the range of 35–60% VO2max or 50–70% HRmax, which corresponds to 3–6 METs [metabolic equivalent = (oxygen consumption/resting oxygen consumption) × 3.5] (Mann et al., 2013). Research indicates that aerobic exercise, such as running, swimming, or cycling, is highly effective in improving MDD (Guszkowska, 2004).

Several large studies have confirmed the antagonistic and placebo effects of aerobic exercise on depressive symptoms. To explore whether a single session of ECT immediately alleviates depression levels, Martin et al. assessed the effect of a single 30-min walk on acute affective responses in patients with MDD. The exercise group demonstrated a significant reduction in negative affective responses and a substantial increase in positive affect levels following exercise compared to the passive control group. Light to moderate intensity walking activated higher levels of positive affective responses (Niedermeier et al., 2021). Studies have shown that short interventions can enhance the effect of a single ECT. Knubben et al. conducted a 10-day walking intervention on patients hospitalized for high levels of MDD. The exercise group showed a more significant reduction in both the Bech-Rafaelsen Melancholy Scale (BRMS) and the Center for Epidemiologic Studies Depression scale (CES-D) scores compared to the control group. Additionally, a higher percentage of patients in the exercise group experienced a reduction of 65 or more points on the BRMS (Knubben et al., 2007). Furthermore, additional studies have assessed interventions over extended periods. For instance, Matthew et al. conducted a 20-week trial comparing the effectiveness of ECT and modified rest and relaxation therapies for MDD. The final results indicated that the exercise group had lower Hamilton Depression Scale (HAMD) scores than the control group, and the depression remission rate was significant (Martiny et al., 2015). Similarly, Josine et al. randomly assigned 141 patients with MDD to either a medication or running exercise group. After 16 weeks, both interventions produced significant reductions in depression symptoms, with no significant difference in efficacy between the two groups. The study found that the running group showed significant physiological improvement compared to the control group. Additionally, the running group experienced weight reduction, improved blood pressure, optimized heart rate, and improved heart rate variability (Verhoeven et al., 2023).

Although studies have tested the effectiveness of ECT, a large number of them have focused on comparing the duration and period of exercise as the main variables. In a 12-week intervention trial, Heinzel et al. compared the effects of high-intensity or low-intensity exercise on the alleviation of depressive symptoms in 120 patients with MDD. After the intervention, it was found that there was no significant difference between the groups in terms of Beck Depression Inventory (BDI) and HAMD, indicating that high-intensity exercise did not provide better relief from depression than low-intensity continuous exercise (Heinzel et al., 2022). In the 8-week trial conducted by Li et al., the MICT intervention was administered to 40 depressed patients at a frequency of 60 min, three times per week. This is a shorter-term example. The study found that patients’ HRSD-17 scores were reduced by 50% from baseline. Additionally, the Patient Health Questionnaire (PHQ-9) showed a significant decrease, while the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-QSF) showed a positive improvement (Li et al., 2023). To better characterize the temporal effects of ECT on MDD, Bellón included 18 studies in a systematic review that assessed 1,737 subjects from 8 countries and found that at least 4 weeks of ECT significantly reduced depression scores in patients aged 18–64 years. Meanwhile, selective prevention (i.e., people exposed to risk factors for depression) was associated with lower efficacy of ECT in Asian (Bellón et al., 2021). In conclusion, numerous studies have confirmed the remarkable effectiveness of ECT, AE, and MICT. This type of exercise has positive effects on regulating negative emotions, increasing self-confidence, and improving mental health, which are particularly important for individuals with MDD who struggle with depression (Figure 1).

Figure 1. Biological manifestations of the effects of PA on MDD. Note: ⬆: Facilitation, ⬇: Repression, ▲: Regulation.

Numerous studies have investigated the neural mechanisms of ECT and its effects on MDD. Evidence suggests that MDD is linked to elevated levels of inflammatory factors in the body and brain. However, ECT has been shown to decrease the secretion of pro-inflammatory cytokines, including IL-6 and tumour necrosis factor alpha (TNF-α) (Shih et al., 2013). Meanwhile, the decline of cognitive ability and neuroplasticity in patients with MDD poses a significant threat to their health. It has been widely demonstrated that ECT stimulates the secretion of benign small molecules in brain, including DA, NE, 5-HT, and endorphins, and significantly increases neuroplasticity in MDD patients (Ayari et al., 2023). Individuals’ intracranial release of BDNF after high-volume sustained exercise can repair the symptoms of hippocampal atrophy, which is believed to be the main reason why ECT improves cognitive function in patients with MDD (Hendrikse et al., 2022). In addition to affecting the nervous system, ECT can reduce the release of hormones, glucose, and oils that occur during a depressive state. It also improves the adrenal medulla’s ability to secrete catecholamines, which can help alleviate depressive symptoms (Duncan et al., 1985). Overall, ECT has a significant positive impact on improving physiological indicators and internal mechanisms in patients with MDD and is therefore often recommended as part of a comprehensive treatment program (Figure 2).

Figure 2. Mechanisms of exercise regulation of the intracerebral environment and small molecules in the brain. Note: Brain-Derived Neurotrophic Factor (BDNF), Insulin-Like Growth Factor 1 (IGF-1), IGF-1 Receptors (IGF-1-R), MAPK-Activated Protein Kinase 1 (MARK I), MAPK-Activated Protein Kinase 2 (MARK II), Phosphorylation of MARK II (p-MARK II), Calmodulin Dependent Protein Kinase II (CaMK-II), Insulin Like Growth Factor Receptors (IGFR), Tropomyosin-Related Kinase B (TrkB), TrkB Receptors (TrkB-R), Ras-Induced Senescence 1 (RIS1), Phosphoinositide 3-Kinases (PI3Ks), Mechanistic Target Of Rapamycin (mTOR), 70 kDa Ribosomal S6 Kinase (p70S6K), eIF4E-Binding Protein (4EBP), cAMP-Response Element Binding Protein (CREB), Phosphorylation of CREB (p-CREB). PA induces hippocampal production of IGF-1 and enhances hippocampal synaptic plasticity through BDNF downstream signaling mechanisms, including CAMK II, MARK I and p-MAPK II signal cascades. The interaction of IGF-1, BDNF mRNA and pro-BDNF protein occurs at the postsynaptic membrane.

Explosive interval training

EIT is typically categorized as vigorous physical activity (VPA), with high intensity. >80% of maximum heart rate, 70% of maximum oxygen uptake, and more than 6 METs. During EIT, the body consumes energy substances such as creatine phosphate and glycogen through the anaerobic energy supply system, which includes the phosphagen and glycolytic systems, to supply sufficient ATP to meet the body’s needs. When engaging in EIT, the human body continuously consumes energy sources such as phosphocreatine and glycogen through the anaerobic energy supply system, including the Phosphagen System and Glycolytic System. This process supplies sufficient ATP to meet the body’s energy demand for a short period of time. However, it also results in a higher level of lactic acid. Numerous studies have investigated the efficacy differences between EIT and other forms of exercise in treating MDD. One of the most representative forms is High-Intensity Interval Training (HIIT) or Sprint Interval Training (SIT). The exercise format of HIIT, SIT usually refers to high intensity sprints of 80–95% HRmax/70–85% VO2max for 30s to 2 min, interspersed with low intensity intermittent recovery of 55–65% HRmax/40–55% VO2max for 1 min 30s to 4 min, during which MET levels can vary from 6 to 15 METs (Mann et al., 2013). Due to its time efficiency and greater impact on cardiorespiratory fitness, HIIT has been extensively researched in comparison to MICT regarding its effects on psychological well-being, physical fitness, and exercise enjoyment for both healthy individuals and those with MDD.

Several lines of evidence suggest that EIT has a positive moderating effect on the mental health and emotional state of people with MDD. Matthew et al. found through a systematic evaluation of multiple studies that the majority of patients produced favorable affective responses after a single session of EIT compared to a blank control group, and this effect was consistent across different types of affective states, exercise environments (Self-Selected/Imposed/Outdoor/Indoor), and participant characteristics (Bourke et al., 2022). Rebecca et al. conducted a comprehensive meta-analysis of 85 studies, which included a large number of people of all ages, as well as overweight and metabolically disordered patients. The results showed that HIIT intervention was effective compared to an inactive control group across all populations. HIIT at a frequency of at least 2 times/week for 2 weeks or more reduced the risk of depression, anxiety, other negative mood factors, and MDD. HIIT improved cardiorespiratory fitness, body composition, blood glucose and lipid concentrations, arterial compliance and vascular function, cardiac function and reserve, markers of inflammation in the brain and body, exercise capacity, and muscle mass significantly more than other treatments. No acute injuries were reported in any of the studies, and the average adherence rate was over 80% (Martland et al., 2020).

Although EIT has been shown to promote mental health, it is still inconclusive whether its effects are superior to those of other PA. Alice et al. conducted 12-week AE and SIT interventions for patients with MDD and found that BDI scores of the subjects in both groups were significantly reduced. However, there was no significant difference between the groups, although SIT saved time and achieved the same effect as AE. There was no significant difference between the groups (Minghetti et al., 2018). The results may be attributed to the short intervention period. Generally, the duration of exercise can cause differences in individual physiological and psychological indicators. Markus et al. obtained similar results through a 35-week experiment. They divided 50 MDD patients into two groups including SIT and ECT, compared the two groups of patients in the after-training period for changes in indicators of positive affective response, self-perceived health, cardiorespiratory health, and level of depressive symptoms. Finally, both groups showed improvement in all metrics at the end of the intervention, except for autonomic exercise motivation, which did not significantly change from baseline. However, there were no significant differences between the groups, indicating a significant time effect. However, the ECT group was slightly more likely to reach the recommended level of physical activity after the intervention compared to the SIT group (Gerber et al., 2018). This may be due to the fact that ECT has a simpler training format and delivery conditions than SIT and a lower barrier, making it more suitable for first-time exercisers to develop exercise adherence (Figure 3).

Figure 3. Effects of pa on structural plasticity and neuroelectrical activity of the brain in MDD. Note: ⬆: Facilitation, ⬇: Repression. Amplitude of Low-Frequency Fluctuations (ALFF), Late Positive Potential (LPP), Motor Evoked Potentials (MEPs), Total Mean Frequency (TMF), Nucleus Accumbens (NAc), Prefrontal Cortex (PFC).

However, other studies have shown that EIT is more effective than other PAs for MDD. For example, Björg compared the efficacy of conventional medication (310), low-intensity ECT (106), moderate-intensity ECT (105), and EIT (99) in a one-year randomized controlled trial of 620 patients aged 18–67 years with MDD. The results showed that during the first 2 months, conventional medication significantly reduced patients’ scores on the Montgomery-Asberg Depression Rating Scale (MADRS). However, starting at 5 months, the three exercise groups outperformed the medication group in intervening on depressive symptoms. At the end of 1 year, the EIT group not only had the lowest MADRS score, but also the highest quality of life score based on the MOS item Short Form Health Survey (SF-36). At the same time, adherence to low-intensity ECT was the highest. This suggests that EIT improves the effectiveness of rehabilitation in MDD patients (Helgadóttir et al., 2017). To test this claim, Yolanda divided 67 COVID-19 matched adults into two groups, administered the HIIT and MICT, and assessed differences in anxiety, stress, and resilience using the BDI, State–Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS-10), Connor-Davidson Resilience Scale (CD-RISC) to assess differences between the two groups of subjects in anxiety, depression, stress, and mental toughness. The results showed that after 40 weeks of intervention, stress and anxiety symptoms were significantly reduced in both groups of subjects. However, the HIIT group had lower levels of depression and better mental toughness than the MICT group (Borrega-Mouquinho et al., 2021). To validate the temporal effect profile of HIIT, Nicole demonstrated in a systematic review of 366 patients with MDD that at least 4 weeks of HIIT significantly reduced depressive symptoms such as suicidal ideation and behavior, negative mood, and limitations in physiological functioning, and that 8 weeks of HIIT was superior to MICT in improving life satisfaction, social functioning, cognitive ability, and self-control, and there was no difference in adherence. MICT was superior to HIIT in improving life satisfaction, social functioning, cognitive ability, and self-control, and there was no significant difference in adherence (Korman et al., 2020). In response to the controversies in the aforementioned studies, Rebecca systematically summarized the mental health outcomes of HIIT based on her previous research. The results showed that both HIIT and MICT were effective in terms of acute mental health changes. However, there was no significant difference between the two groups, and only one study reported a more significant outcome for HIIT. Regarding long-term mental health changes, HIIT demonstrated greater reductions in anxiety levels between 3 months and 5 years. Additionally, HIIT showed moderate improvements in depression, anxiety, and psychological stress, but not superior to MICT (Martland et al., 2022). In conclusion, the available evidence suggests that there is no significant difference between HIIT and MICT in terms of improving mental health. However, it is important to consider the heterogeneous results of a small number of studies. Therefore, further research is needed to examine the temporal relationship between exercise intensity in MDD interventions (Figure 4).

Figure 4. Effect of PA on the release of neurotransmitters and small molecules in MDD. Note: ⬆: Facilitation, ⬇: Repression, ▲: Regulation. Glutathione Peroxidase (GPx), Oxidative Stress (SOD), Norepinephrine (NE), Dopamine (DA), 5-Hydroxytryptamine (5-HT), Glutamic Acid (Glu), γ-Aminobutyric Acid (GABA), Vascular Endothelial Growth Factor (VEGF), Mammalian Target Of Rapamycin (mTOR), Insulin-Like Growth Factor 1 (IGF-1), Brain-Derived Neurotrophic Factor (BDNF), Fibroblast Growth Factor 2 (FGF-2), Medium Spiny Neurons (MSNs), Nucleus Accumbens (NAc), Glutamate Decarboxylase 2 (GAD2), Substantia Nigra Pars Reticulate (SNR), Prefrontal Cortex (PFC).

So far, the superiority of EIT in MDD intervention is still inconclusive, and the heterogeneity of results from different studies is large. Therefore, this study explains the phenomenon from the perspective of neural mechanisms. EIT stimulate the release of neurotransmitters such as DA, NE, and BDNF, activate the growth of new neurons, and increase inter-synaptic communication, resulting in an increase in parasympathetic activity. This not only improves an individual’s mood and attention span but also decreases their resting heart rate, increasing their cardiac reserve (Zimmer et al., 2016; ROSS et al., 2019; Shirvani et al., 2019). ECT may also promote the secretion of such transmitters, but to a lesser extent. In the endocrine system, it has been found that acute EIT elevates cortisol and testosterone secretion levels to a greater extent than ECT (Dote-Montero et al., 2021). Under certain circumstances, moderate cortisol secretion can enhance the body’s ability to adapt. However, if cortisol remains elevated for an extended period, it can negatively impact the brain and nervous system. EIT helps the body regulate its levels and concentrations more effectively. From a circulatory perspective, the EIT process is typically accompanied by a rapid increase in blood flow and oxygen demand. If the body’s needs are not met within a short period of time, this can result in insufficient blood supply and oxygen deficit (Hill et al., 2008). ECT only accelerate blood flow and do not cause these conditions. Therefore, EIT results in a more significant increase in the amount of oxygen in the brain, especially after a sustained period. Overall, EIT has been shown to improve depressive symptoms, cognitive function, and brain plasticity in patients with MDD, but the specific dosage needs to be adjusted according to individual physiological factors and subjective readiness, such as HIIT or SIT.

Resistance strength training

Resistance strength training (RST) is a type of exercise that involves working against resistance to enhance muscle strength and volume. RST typically includes weights, resistance bands, or bodyweight exercises like push-ups or squats (Westcott, 2012). In general, the energy supply system of RST heavily relies on the body’s anaerobic energy system. This system uses stored energy in the form of ATP and phosphocreatine to provide energy for short bursts of intense activity. As the exercise continues, the body also relies on glycogen stored in the muscles to provide energy. Acute or prolonged Resistance strength training not only boosts metabolic levels and slows down the body’s aging process, but it can also effectively reduce negative emotions such as anxiety and depression (Hill et al., 2008; McLeod et al., 2019). Compared to MICT/HIIT, there are fewer MDD studies related to the design of RST. However, evidence suggests that RST can be an effective tool on its own or in combination with medication, and can have a positive effect on interventions for depression.

Currently, although there are few studies on the relationship between MDD and RST, evidence suggests that RST can be an effective tool, either alone or in combination with medication. For instance, Joseph et al. conducted a 12-month intervention in which 50 MDD male patients were randomly assigned to an RST group or an attention-training group. Results showed that at the end of the intervention, the RST group not only had significantly lower scores on the Quick Inventory of Depression Symptomology (QIDS) than the attention training group, but also had additional improvements in body composition, including muscle density, adiposity, and BMI (Ciccolo et al., 2022). To compare the effects of RST with other exercises on MDD, Helena extended the resistance strength training to older adults and compared the effects of 12 weeks of ECT and RST on a small sample of older adults with MDD (n = 27) using HAMD. The final results showed that both ECT and RST significantly reduced depression levels in older adults by approximately 50%. However, there was no significant difference between the two groups (Moraes et al., 2020). Krogh found similar results in a 12-month cohort study. After comparing the differences in the effects of MICT and RST on mental status and motor function in patients with MDD, he found that from month 4, both groups showed a significant decrease in HAMD and Hamilton Anxiety Scale (HAMA) scores and an increase in Mindful Attention Awareness Scale (MAAS)-based positive mindfulness. At the end of 12 months, the mental status of patients in both groups improved, and although there was no significant difference between the groups, the RST group had better strength qualities and BMI than the MICT group (Krogh et al., 2009). To characterize the timeliness of RST interventions for MDD, Barahona found through a systematic evaluation involving 768 patients with MDD that the effect of RST on improving depression levels was significant from at least 10 weeks and was accompanied by reductions in negative emotions such as anxiety, stress, sadness, and hostility, and increases in self-esteem, self-efficacy, and self-control (Barahona-Fuentes et al., 2021). The above results suggest that RST has similar effects on improving depressive symptoms and mental health in MDD patients as ECT and EIT, but the improvement effects on physiological functions, including body composition, strength quality, and exercise capacity, are more significant. Meanwhile, the effective period of RST is longer than other exercises, so it may not be conducive to the development of exercise adherence.

Although there is insufficient evidence to confirm that RST is superior to other exercises in improving MDD, RST is superior in improving patients’ motivation to exercise. For example, core symptoms of patients with MDD include a lack of interest and motivation, which in adults can lead to phenomena such as difficulty going to work on a daily basis or a low rate of return to work. For this reason, the mental health of workers in enterprises has long been a major concern of the WHO and international trade union organizations (Evans-Lacko and Knapp, 2016). Some studies have shown that RST is an effective modality that can significantly improve an individual’s level of depression and motivation to exercise. Karen et al. conducted a study on the return-to-work attendance of 5,996 patients with MDD after receiving usual care, cognitive therapy, medication, combined psychological and medication, and RST interventions. The study found that supervised RST significantly reduced sickness absence in patients with MDD and was superior to ECT and MBT (Nieuwenhuijsen et al., 2020). Meyer explained the superiority of RST in improving motivation to exercise in MDD patients from a psychological perspective in a 26-week cohort study. He found that at the end of the experiment, the RST group not only had lower levels of self-reported and clinically identified depression, but also had higher exercise adherence than the RCT control group. To explain this phenomenon, they reported exercise adherence at weeks 8, 16, and 24 and found that it increased from 90 to 93 and 98% in the RST group, respectively, and was accompanied by higher middle cerebral artery (MCA) blood flow velocity, electrical conductivity, and muscle circumference. No significant changes were observed in the RCT group. In contrast to the RST group, the RST group used a progressive training regimen, i.e., the number of sets and intensity of the training gradually increased as the individual’s physical fitness changed, thus triggering the Hawthorne effect in the patients, i.e., individuals tended to be willing to continue to persevere and increase the level of difficulty when they performed a task that was within their ability range and became motivated. In the RST group in this study, patients initially performed only a few sets of straight arm flexion and extension, and due to the specificity of RST, significant muscle hypertrophy was observed at the end of each training session. Later, when the training intensity was gradually increased, the “muscular hypertrophy” induced by the strength training became more significant, thus motivating the patients to complete the entire training program involving multiple movements at once, which is also considered to be the main reason why RST can more effectively stimulate the exercise motivation of patients with MDD (Meyer et al., 2024). Despite the significant benefits of RST in improving exercise adherence, the number of studies of RST in MDD is still very limited due to the large space, equipment, and technician requirements for implementation.

From a neural mechanism perspective, the antidepressant effects of RST may result from various effects on different aspects of the patient’s nervous system, some of which are similar to ECT and others that are different. Studies have shown that RST also increases the positive release of certain transmitters and small molecules in the brain, similar to other exercises, which in turn promotes neuronal growth. There is evidence that RST modulates plasticity changes in the Central Nervous System (CNS) and improves cognitive functioning (Chow et al., 2021). For instance, Majid discovered that administering RST to college students with MDD for 10 weeks resulted in a decrease in C-reactive protein, an increase in plasma levels of 5-HT and NE, and a moderate decrease in cortisol levels. These changes in monoamine transmitters were strongly associated with exercise-induced improvements in MDD (Khorvash et al., 2012). Not only that, but it has also been shown that prolonged RST is associated with a decrease in inflammatory factors in the brain, such as IL-6, TNF-alpha, and C-reactive protein (CRP), which are involved in the immune system’s or the liver’s response to inflammation, respectively. Elevated levels of these factors have a direct impact on the risk of depression, and regular RST reduces the secretion of these substances.

Mind–body training

Mind–body trainings (MBT) are physical activities designed to improve the connection between the mind and body, promoting relaxation, stress reduction, and positive thinking. MBT combine physical movement, breathing techniques, and mental focus to achieve these results. MBE, such as Tai Chi, Yoga, Qigong, or Mindfulness meditation programs, are characterized by a focus on breathing and positive thinking. These exercises often emphasize breath control and mental focus (Stringer, 2021). This exercise type is typically low to moderate intensity, with an intensity range of 50–70% HRmax/30–50% VO2max or 2–3 METs. It does not require a high level of physical exertion and is therefore suitable for individuals of all fitness levels. This type of exercise is widely popular and non-competitive (Saeed et al., 2019). Numerous physical and mental exercises involve whole-body movement and promote flexibility, balance, and coordination. To date, an increasing number of studies have shown that physical and mental exercise can effectively alleviate symptoms of depression.

A significant body of evidence suggests that MBT can be used as an adjunctive therapy to improve depressive symptoms in people with MDD and in various populations. In a meta-analysis, Ashok et al. evaluated the effects of Tai Chi on people with MDD. The results showed that exercise and yoga as adjunctive treatments could mildly reduce depression levels compared to controls, while Tai Chi lacked sufficient evidence to support its effect (Seshadri et al., 2020). Juyoung et al. evaluated the effects of yoga, tai chi, and qigong on depression, anxiety, and psychological well-being in patients with MDD. They found that MBT interventions resulted in positive outcomes, including reductions in physical pain and psychological distress, as well as improvements in physical functioning (Park et al., 2020). To validate this claim, Saeed et al. conducted a study on older adults living in nursing homes. They compared the effects of a Tai Chi intervention with usual care on the depression levels of the participants. The study found that the Tai Chi intervention group showed a significant improvement in depression levels after 12 and 24 weeks compared to the usual care group (Saeed et al., 2010). To compare the time-lapse study of MBT in antidepressant effects, Zhang et al. conducted a systematic evaluation of the effects of tai chi and qigong exercises on depression and anxiety levels of MDD patients. The study found that all subjects experienced a sustained decrease in depression and anxiety levels over the course of 57 weeks, from week 1 to week 57(Zhang et al., 2022). Effective coping strategies are necessary for individuals in special populations and those experiencing stress in modern work life. Maddux conducted a 16-week yoga intervention for employees with high levels of work-related stress and found that after 8 weeks, the yoga group showed a significant reduction in stress and negativity and a significant increase in well-being, while the blank control group showed no significant change. To re-examine the efficacy of MBT, Maddux also administered yoga to a blank control group for an additional 8 weeks and found at week 16 that the original control group also showed significant reductions in depression, stress, anxiety, and insomnia after 8 weeks of yoga (Maddux et al., 2018). Furthermore, various studies have shown the significant antidepressant effects of mind–body training in separate experiments with female college students, drug addicts, and chronic pain sufferers, among others (Liu et al., 2020; Wen et al., 2022).

From a neural mechanism perspective, studies have consistently shown that MBT has a modulatory effect on brain environment and neurotransmitters in patients with MDD. Like VPA, MBT reduces sympathetic nervous system excitability and increases parasympathetic nervous system activity, resulting in reduced stress and anxiety (Kandola et al., 2019). In terms of neurotransmitter release, several studies have demonstrated that yoga for at least 12 weeks effectively improves imbalances in patients’ positive serotonin levels and results in significant increases in levels of DA, 5-HT, BDNF and GABA (You and Ogawa, 2020; Zhang et al., 2021). In addition, MBT increases the production of endorphins in the brain and spinal cord, enhances neuroplasticity to improve the ability of neurons to form new connections with each other and adapt to change (Wang et al., 2017). Some studies have found that MBT may modulate biological processes related to depression, such as inflammation, oxidative stress, and the endocrine system. Dilorom et al. found significant reductions in IL-6, TNF-alpha, and CRP levels through systematic analyses of yoga for at least 2 weeks (Djalilova et al., 2019). Di et al. conducted a study that validated similar results. They found that 12 weeks of qigong practice increased hippocampal volume and decreased peripheral IL-6 levels compared to stretching exercises. As a result, reaction speed and sustained attention improved (Qi et al., 2021). Although these studies did not directly measure inflammatory factor concentrations in the brain, it is believed that changes in peripheral inflammation may also indicate changes in CNS inflammation. However, further research is needed to confirm this. Additionally, there is evidence that MBT may improve brain structure. Kong et al. found that regular practice of physical and mental exercise increased the volume of the hippocampus in patients with depression (Kong, 2021). In a previous study, Tao et al. discovered that 12 weeks of Ba Duan Jin and Tai Chi Chuan significantly increased gray matter volume in the insula, medial temporal lobe, and nucleus accumbens in older subjects. This was accompanied by improved memory and cognitive functioning (Tao et al., 2017). Meanwhile, MBT has been shown to activate brain regions associated with MDD patients, promote behavioral adaptive changes, and maintain the integrity of white matter volume, thereby improving brain neural processing and delaying cognitive deterioration (Zhao et al., 2020). Additionally, it modulates brain neural activity and functional connectivity in various regions, including PFC, the hippocampus/medial temporal lobe, the lateral temporal lobe, the insula, and the cingulate gyrus, as well as in brain networks such as the cognitive control network and the default mode network. Not only that, MBT improves cerebral blood flow (CBF) abnormalities in MDD patients (Liu et al., 2022), which may account for its beneficial effects on cognitive functions such as mood, attention, memory, and self-awareness (Zhang et al., 2021).

Dose characterization of exercise for improving executive function in MDD

Higher cognitive functioning refers to the ability of humans to process information, make decisions, and control behavior in complex environments. It enables thinking, learning, memory, attention, and judgment, among other cognitive activities (Liu et al., 2022). These functions are primarily mediated by PFC of the brain. They reflect the characteristics and states of objective things and their interconnectedness, revealing their meaning and role to people (Tyng et al., 2017). Higher cognitive functions are significant and have a great influence on individuals. They aid in adapting to different situations, improving learning and work efficiency, enhancing self-regulation and social interaction, and improving the quality of life (Xiong et al., 2020). However, patients with MDD exhibit multifaceted abnormalities in higher cognitive functions, primarily manifested as executive function degradation (Rock et al., 2014). These cognitive impairments can impact patients’ daily life, social functioning, and treatment outcomes (Bernhardt et al., 2021).

Inhibitory control

Executive functions refer to a set of higher cognitive processes that allow individuals to intentionally regulate their thoughts, behaviors, and emotions in order to adapt to complex and changing environments (Diamond, 2013). These processes include inhibitory function, working memory, and cognitive flexibility.

Research has demonstrated that exercise can improve response inhibition and promote adaptive behavioral changes in individuals with MDD (Ahn and Kim, 2023). However, the effectiveness of exercise may be influenced by factors such as intensity, frequency, duration, and type of exercise (Greer et al., 2015). In a 6-week randomized controlled trial, Imboden divided 52 patients with MDD into two groups and administered ECT and MBT, respectively, and found that at the end of 6 weeks, the Go-No-Go task scores of the MBT group stabilized at around 393.9, while the scores of the ECT group increased from 405.5 to 443.9, which was a significant difference between the two groups. This also suggests that ECT may have a more significant effect on improving inhibitory control in MDD patients (Imboden et al., 2020).

In addition to the short-term study, Olson extended the PA intervention cycle and again found similar results. They discovered that an 8-week MICT intervention improved information processing accuracy by 1.4% in MDD patients, while the control group experienced a 2% decrease. Additionally, the exercise group experienced a decrease in reaction time by 73.45 ms, while the control group experienced an increase of 13.76 ms (Olson et al., 2017). Not only that, Alderman evaluated the effect of MBT combined with an ECT regimen on inhibitory function in 52 patients with MDD in an 8-week longitudinal study. The results showed that after the patients’ intervention, the correct rate of congruent trials increased from 96.8% at baseline to 98.5%, and the reaction time decreased from 319.5 ms to 301.2 ms. At the same time, the correct rate of incongruent trials increased from 86.1% at baseline to 89.2%, and the reaction time decreased from 390.0 ms to 373.0 ms, and all indicators showed statistically significant differences. In addition, depression and negative rumination were significantly suppressed in all patients (Alderman et al., 2016). Brüchle et al. conducted an 18-month experiment and found that the STROOP test, Go-No Go, and Tower of London scores of MDD patients significantly improved at the end of the training. This implies that long-term physical activity significantly improved the executive and inhibitory functioning of the patients (Brüchle et al., 2021).

Although PA has been shown to enhance multiple dimensions of executive functioning in patients with MDD, it is important to note that this may be due to differences in the cognitive testing tasks used in various experiments. Nevertheless, it is worth acknowledging that PA has been widely demonstrated to be an effective means of combating cognitive decline in patients with MDD.

Working memory

Individuals with MDD often report declines in working memory and attention, as evidenced by difficulties in memory encoding and thought retrieval, particularly the inability to retain and manipulate a limited amount of information for short periods of time (Semkovska et al., 2019).

PA has been demonstrated to be an effective method of mitigating memory and attention decline induced by MDD, but the current evidence is inconclusive. Buschert compared the effects of ECT with tetracyclic antidepressants on executive function in 38 patients with MDD in a short-term (4 weeks) randomized controlled trial. The results showed that at the end of the intervention, scores on the N-Back task, short-term verbal memory, and reaction time showed a significant upward trend in both groups compared to baseline. However, the differences between the two groups were not statistically significant. This also suggests that short-term moderate PA improves patients’ working memory more effectively than pharmacological intervention, but with fewer side effects (Buschert et al., 2019). Zhang and Chen (2019) conducted an 8-week ECT intervention and observed improvements in memory and attention among 125 patients with MDD. The Wechsler Memory Scale (WMS) results at weeks 4 and 8 showed moderate to substantial improvements in memory and attention, respectively (Zhang and Chen, 2019).

In addition to short-term studies, Brüchle found a temporary positive effect of ECT on working memory in MDD patients in an 18-month long-term intervention study. After 4 weeks, the patients showed an increase in reaction time in the 2-Back versus cross-modal matching task, but no significant change in accuracy. At week 8, accuracy on both tasks improved from 48.96% vs. 52.89 to 53.35% vs. 54.78%, respectively. However, there was no significant change in BDI-based depression scores. In the period up to the end of the experiment, the patients’ depression levels continued to decrease, but the scores on the two memory tasks did not change significantly. This suggests that in the short term, PA has a more significant improvement effect on memory function and attention than antidepressant effects in patients with MDD (Brüchle et al., 2021). In contrast, Katharina et al.’s experiment overwhelmingly refuted this claim. They found that patients with MDD did not show significant changes in attention and alertness based on the D2 Test of Attention after 8 weeks of indoor rock-climbing, despite a reduction in depression levels (Luttenberger et al., 2015). Another trial with a longer duration came to similar conclusions. Benson et al. compared 202 middle-aged and elderly MDD patients after 16 weeks of exercise or medication. It was found that the patients’ executive function improved, but there was no significant change in working memory perception on the Animal Naming Tes.

In conclusion, there is currently insufficient evidence to support the benefits of physical activity on memory and attention in MDD, but there is still much room for further exploration.

Cognitive flexibility

Cognitive flexibility is a crucial aspect of an individual’s judgment and thinking (Friedman et al., 2018), and it is negatively affected by the loss of BDNF due to the buildup of neuroinflammatory substances in patients with MDD. This can result in a decline in their cognitive flexibility abilities, including vision and language skills (Lima Giacobbo et al., 2019).

Although PA has been shown to improve the condition, its effects may vary depending on the type of the exercise (Morales et al., 2024). To test this claim, Viola compared the difference between the effects of ECT and MBT on cognitive flexibility in people with MDD in a 4-week longitudinal study. The results showed that the ECT group had higher scores than the MBT group on the Task Switching and Exogenous Cueing paradigms at the end of the intervention, but there was no major difference in HAMD scores between the two groups (Oertel-Knöchel et al., 2014). Similar results were found in a longer-term study in which Krogh extended the PA period to 3 months and randomized 56 patients with MDD into two groups, ECT and MBT, and found that at the end of the intervention, the ECT group’s accuracy rates on the Rey Complex Figure Test and the Digit Symbol Test for assessing visuospatial cognition increased from 56.3 and 89.5% to 61 and 93.7%, respectively, which was 1.2 and 4.7% higher than that of the MBT group. However, there was no significant difference in the BDI scores (Krogh et al., 2012). These results suggest that ECT and MBT have similar effects on improving depressive symptoms in MDD patients, but the facilitating effect on cognitive flexibility is more significant.

However, the results described above are also heterogeneous in a subset of studies. Some of the evidence suggests that ECT and MBT are similarly effective in improving MDD, while RST and EIT may be more effective than the former. Krogh, in another prospective randomized controlled trial, divided 165 patients with MDD into three groups and administered 4 months of ECT, RST, and MBT and compared the effects of the different PAs on the patients’ levels of depression and cognitive flexibility. It was found that during the first 8 weeks, HAMD scores decreased in all three groups, but there was no significant difference in the accuracy of cognitive tasks. After 12 weeks, the accuracy of the Wisconsin Card Sorting Test (WCST) in the RST group became progressively higher than in the other two groups. At the end of 4 months, the Buschke Selective Reminding Test, WCST accuracy in the RST group was already significantly higher than that of the other two groups. The HAMD scores were similar to those of the ECT and were higher than those of the MBT (Krogh et al., 2009). In addition, Brondino compared the effects of ECT and EIT on cognitive flexibility such as processing speed, similarity recognition, verbal fluency, auditory transitions and learning, complex spatial localization, and logical reasoning in a meta-analysis of 637 patients with MDD. The effect of EIT on improving cognitive flexibility was examined. The results showed that both EIT and ECT had similar effects on processing speed, verbal fluency, and auditory transitions and learning, but EIT was more effective than ECT in improving similarity recognition, complex spatial localization, and logical reasoning after more than 10 weeks of treatment, and the heterogeneity of the results was less (Brondino et al., 2017).

In conclusion, the available research suggests that there is a significant positive effect of PA on cognitive flexibility in patients with MDD, but this may be influenced by differences in the type of exercise. Most of the current evidence suggests that EIT with RST is more effective than ECT and MBT, and the present study speculates that the main reason may be due to the fact that the intensity of the exercise is higher in the former than in the latter. Nevertheless, more evidence is needed in the future to confirm the dosage profile of this PA in improving cognitive flexibility in patients with MDD.

Correlation of exercise patterns with sleep improvement in MDD

Sleep behavior is a fundamental physiological need of the human body. MDD can significantly impact human sleep, creating a complex and bidirectional phenomenon. Individuals with MDD may experience symptoms such as difficulty falling asleep, frequent night awakenings, or early morning awakenings, which can increase the likelihood of sleep disorders and worsen depressive symptoms. This creates a vicious cycle that is difficult to break. These problems are commonly observed in patients with MDD. Firstly, there are abnormal changes in sleep structure, including a decrease in the amount of deep (slow-wave) sleep and an increase in the amount of light rapid eyes movement sleep (REM)(Vahia, 2013). Secondly, abnormal sleep states are manifested in the phenomena of difficulty in falling asleep, excessive